scholarly journals Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus

2018 ◽  
Author(s):  
Stephen D. Glasgow ◽  
Simon Labrecque ◽  
Ian V. Beamish ◽  
Sarah Aufmkolk ◽  
Julien Gibon ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Guidance Cue ◽  
Term Potentiation ◽  
Nmdar Activation ◽  
Genetic Deletion ◽  
Adult Hippocampus ◽  
Activity Dependent

AbstractDynamic trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, however the identity of key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion of the chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, we show that netrin-1 expression by excitatory neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult hippocampus. Further, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent recruitment of GluA1-containing AMPARs, promoting the maturation of immature or nascent synapses. These findings identify a central role for activity-dependent release of netrin-1 as a critical effector of synaptic plasticity in the adult hippocampus.

scholarly journals GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity

2003 ◽  
Vol 358 (1432) ◽  
pp. 715-720 ◽  
Author(s):  
Fabrice Duprat ◽  
Michael Daw ◽  
Wonil Lim ◽  
Graham Collingridge ◽  
John Isaac
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Protein Interactions ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Synaptic Proteins ◽  
Mammalian Brain ◽  
Protein Protein Interactions ◽  
Term Potentiation

AMPA-type glutamate receptors mediate most fast excitatory synaptic transmissions in the mammalian brain. They are critically involved in the expression of long-term potentiation and long-term depression, forms of synaptic plasticity that are thought to underlie learning and memory. A number of synaptic proteins have been identified that interact with the intracellular C-termini of AMPA receptor subunits. Here, we review recent studies and present new experimental data on the roles of these interacting proteins in regulating the AMPA receptor function during basal synaptic transmission and plasticity.

scholarly journals Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus

2010 ◽  
Vol 103 (1) ◽  
pp. 479-489 ◽  
Author(s):  
Hey-Kyoung Lee ◽  
Kogo Takamiya ◽  
Kaiwen He ◽  
Lihua Song ◽  
Richard L. Huganir
Keyword(s):  
Synaptic Plasticity ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Phosphorylation Sites ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Ampa Receptor Subunit ◽  
Glur1 Subunit ◽  
Activity Dependent

Activity-dependent changes in excitatory synaptic transmission in the CNS have been shown to depend on the regulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). In particular, several lines of evidence suggest that reversible phosphorylation of AMPAR subunit glutamate receptor 1 (GluR1, also referred to as GluA1 or GluR-A) plays a role in long-term potentiation (LTP) and long-term depression (LTD). We previously reported that regulation of serines (S) 831 and 845 on the GluR1 subunit may play a critical role in bidirectional synaptic plasticity in the Schaffer collateral inputs to CA1. Specifically, gene knockin mice lacking both S831 and S845 phosphorylation sites (“double phosphomutants”), where both serine residues were replaced by alanines (A), showed a faster decaying LTP and a deficit in LTD. To determine which of the two phosphorylation sites was responsible for the phenotype, we have now generated two lines of gene knockin mice: one that specifically lacks S831 (S831A mutants) and another that lacks only S845 (S845A mutants). We found that S831A mutants display normal LTP and LTD, whereas S845A mutants show a specific deficit in LTD. Taken together with our previous results from the “double phosphomutants,” our data suggest that either S831 or S845 alone may support LTP, whereas the S845 site is critical for LTD expression.

scholarly journals PDZ protein mediated activity-dependent LTP/LTD developmental switch at rat retinocollicular synapses

2010 ◽  
Vol 298 (6) ◽  
pp. C1572-C1582 ◽  
Author(s):  
Lei Xue ◽  
Fan Zhang ◽  
Xianhua Chen ◽  
Junji Lin ◽  
Jian Shi
Keyword(s):  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Basic Mechanism ◽  
Long Term Effects ◽  
Interacting Protein ◽  
Term Potentiation ◽  
Retinal Input ◽  
Pdz Protein ◽  
Activity Dependent

The insertion of amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors into the plasma membrane and removal via internalization are essential for regulating synaptic strength, which underlies the basic mechanism of learning and memory. The retinocollicular pathway undergoes synaptic refinement during development and shows a wide variety of long-term synaptic changes; however, still little is known about its underlying molecular regulation. Here we report a rapid developmental long-term potentiation (LTP)/long-term depression (LTD) switch and its intracellular mechanism at the rat retinocollicular pathway from postnatal day 5 (P5) to P14. Before P9, neurons always exhibited LTP, whereas LTD was observed only after P10. Blockade of GluR2/3-glutamate receptor-interacting protein (GRIP)/AMPA-receptor-binding protein (ABP)/protein interacting with C kinase 1 (PICK1) interactions with pep2-SVKI could sustain the LTP after P10. This suggests that the LTP/LTD switch relied on PDZ protein activities. Selective interruption of GluR2/3-PICK1 binding by pep2-EVKI blocked the long-lasting effects of both LTP and LTD, suggesting a role for PICK1 in the maintenance of long-term synaptic plasticity. Interestingly, synaptic expression of GRIP increased more than twofold from P7 to P11, whereas ABP and PICK1 expression levels remained stable. Blockade of spontaneous retinal input suppressed this increase and abolished the LTP/LTD switch. These results suggest that the increased GRIP synaptic expression may be a key regulatory factor in mediating the activity-dependent developmental LTP/LTD switch, whereas PICK1 may be required for both LTP and LTD to maintain their long-term effects.

scholarly journals Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

2020 ◽  
Author(s):  
Wenting Su ◽  
Jianan Yu ◽  
Min Li ◽  
Ke Wang ◽  
Chang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Synaptic Plasticity ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Motor Skills ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
6 Hydroxydopamine

Abstract Background Parkinson's disease is characterized by abnormal synaptic transmission in the corticostriatal circuit that leads to deficits in motor abilities. Electro-acupuncture has shown to improve the motor behaviors in parkinsonian models. However, the potential mechanisms underlying the electro-acupuncture treatment, specifically in the partial-lesioned model, remain unclear. Methods By utilizing multiple approaches, including electrophysiological, immunohistochemistrical, molecular and behavioral methods, we assessed the effect of electro-acupuncture on the motor dysfunction and striatal synaptic plasticity in a partial-lesioned mouse model induced by intrastriatal injection of 6-hydroxydopamine. Results Electro-acupuncture ameliorated the disrupted gross and fine motor skills in 6-hydroxydopamine-lesioned mice. Notably, electro-acupuncture not only restored the injured corticostriatal long-term potentiation, but also reversed the loss of GluN1-containing NMDA receptors and GluA1-containing AMPA receptors in the striatum. Furthermore, the antagonists selective for AMPA receptors and NMDA receptors blocked the effect of electro-acupuncture on the corticostriatal long-term potentiation in 6-hydroxydopamine-treated mice. Conclusions These data suggest that the postsynaptic glutamate receptors in the striatum undergo the maladaptive changes in the early stage of Parkinson's disease. Electro-acupuncture improves the motor skills via a mechanism involving the modulation of corticostriatal synaptic plasticity and specific glutamate receptors in a partial-lesioned rodent model.

scholarly journals GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130141 ◽  
Author(s):  
Oliver Hardt ◽  
Karim Nader ◽  
Yu-Tian Wang
Keyword(s):  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Molecular Processes ◽  
Short Term ◽  
Receptor Endocytosis ◽  
Term Potentiation ◽  
Short And Long Term ◽  
Activity Dependent

The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

scholarly journals NMDA Receptor Antagonists Reveal Age-Dependent Differences in the Properties of Visual Cortical Plasticity

2008 ◽  
Vol 100 (4) ◽  
pp. 1936-1948 ◽  
Author(s):  
Jacqueline de Marchena ◽  
Adam C. Roberts ◽  
Paul G. Middlebrooks ◽  
Vera Valakh ◽  
Koji Yashiro ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Cortical Plasticity ◽  
Long Term Potentiation ◽  
Underlying Mechanism ◽  
Developmental Shift ◽  
Term Potentiation ◽  
Nmdar Activation ◽  
Visual Cortical

The suggestion that NMDA receptor (NMDAR)-dependent plasticity is subunit specific, with NR2B-types required for long-term depression (LTD) and NR2A-types critical for the induction of long-term potentiation (LTP), has generated much attention and considerable debate. By investigating the suggested subunit-specific roles of NMDARs in the mouse primary visual cortex over development, we report several important findings that clarify the roles of NMDAR subtypes in synaptic plasticity. We observed that LTD was not attenuated by application of ifenprodil, an NR2B-type antagonist, or NVP-AAM007, a less selective NR2A-type antagonist. However, we were surprised that NVP-AAM007 completely blocked adult LTP (postnatal day (P) 45–90), while only modestly affecting juvenile LTP (P21-28). To assess whether this developmental transition reflected an increasing role for NR2A-type receptors with maturity, we characterized the specificity of NVP-AAM007. We found not only that NVP-AAM007 lacks discernable subunit specificity but also that the effects of NVP-AAM077 on LTP could be mimicked using subsaturating concentrations of APV, a global NMDAR antagonist. These results indicate that the effects of NVP-AAM077 on synaptic plasticity are largely explained by nonspecific blockade of NMDARs. Moreover our findings are the first to reveal a developmental increase in the sensitivity of LTP to NMDAR antagonism. We suggest that discrepant reports describing the effect of NVP-AAM077 on LTP may be partially explained by this developmental shift in the properties of LTP. These results indicate that the degree of NMDAR activation required for LTP increases with development, providing insight into a novel underlying mechanism governing the properties of synaptic plasticity.

scholarly journals Elements of a neurobiological theory of the hippocampus: the role of activity-dependent synaptic plasticity in memory

2003 ◽  
Vol 358 (1432) ◽  
pp. 773-786 ◽  
Author(s):  
R. G. M. Morris ◽  
E. I. Moser ◽  
G. Riedel ◽  
S. J. Martin ◽  
J. Sandin ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Cellular Mechanisms ◽  
Memory Processing ◽  
Functional Studies ◽  
Term Potentiation ◽  
Intermediate Storage ◽  
Activity Dependent

The hypothesis that synaptic plasticity is a critical component of the neural mechanisms underlying learning and memory is now widely accepted. In this article, we begin by outlining four criteria for evaluating the ‘synaptic plasticity and memory (SPM)’ hypothesis. We then attempt to lay the foundations for a specific neurobiological theory of hippocampal (HPC) function in which activity-dependent synaptic plasticity, such as long-term potentiation (LTP), plays a key part in the forms of memory mediated by this brain structure. HPC memory can, like other forms of memory, be divided into four processes: encoding, storage, consolidation and retrieval. We argue that synaptic plasticity is critical for the encoding and intermediate storage of memory traces that are automatically recorded in the hippocampus. These traces decay, but are sometimes retained by a process of cellular consolidation. However, we also argue that HPC synaptic plasticity is not involved in memory retrieval, and is unlikely to be involved in systems-level consolidation that depends on HPC-neocortical interactions, although neocortical synaptic plasticity does play a part. The information that has emerged from the worldwide focus on the mechanisms of induction and expression of plasticity at individual synapses has been very valuable in functional studies. Progress towards a comprehensive understanding of memory processing will also depend on the analysis of these synaptic changes within the context of a wider range of systems-level and cellular mechanisms of neuronal transmission and plasticity.

scholarly journals Regulation of NMDA receptor Ca2+ signalling and synaptic plasticity

2009 ◽  
Vol 37 (6) ◽  
pp. 1369-1374 ◽  
Author(s):  
C. Geoffrey Lau ◽  
Koichi Takeuchi ◽  
Alma Rodenas-Ruano ◽  
Yukihiro Takayasu ◽  
Jessica Murphy ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Extracellular Signals ◽  
Term Potentiation ◽  
A Cell ◽  
Nmdar Subunit ◽  
Higher Cognitive Functions ◽  
Activity Dependent

NMDARs (N-methyl-D-aspartate receptors) are critical for synaptic function throughout the CNS (central nervous system). NMDAR-mediated Ca2+ influx is implicated in neuronal differentiation, neuronal migration, synaptogenesis, structural remodelling, long-lasting forms of synaptic plasticity and higher cognitive functions. NMDAR-mediated Ca2+ signalling in dendritic spines is not static, but can be remodelled in a cell- and synapse-specific manner by NMDAR subunit composition, protein kinases and neuronal activity during development and in response to sensory experience. Recent evidence indicates that Ca2+ permeability of neuronal NMDARs, NMDAR-mediated Ca2+ signalling in spines and induction of NMDAR-dependent LTP (long-term potentiation) at hippocampal Schaffer collateral–CA1 synapses are under control of the cAMP/PKA (protein kinase A) signalling cascade. Thus, by enhancing Ca2+ influx through NMDARs in spines, PKA can regulate the induction of LTP. An emerging concept is that activity-dependent regulation of NMDAR-mediated Ca2+ signalling by PKA and by extracellular signals that modulate cAMP or protein phosphatases at synaptic sites provides a dynamic and potentially powerful mechanism for bi-directional regulation of synaptic efficacy and remodelling.

scholarly journals A Multisubcellular Compartment Model of AMPA Receptor Trafficking for Neuromodulation of Hebbian Synaptic Plasticity

2021 ◽  
Vol 13 ◽  
Author(s):  
Stefan Mihalas ◽  
Alvaro Ardiles ◽  
Kaiwen He ◽  
Adrian Palacios ◽  
Alfredo Kirkwood
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptors ◽  
Compartment Model ◽  
Long Term Potentiation ◽  
Reverse Direction ◽  
Term Potentiation ◽  
Simple Kinetic Model ◽  
Ampar Trafficking ◽  
Central Synapses

Neuromodulation can profoundly impact the gain and polarity of postsynaptic changes in Hebbian synaptic plasticity. An emerging pattern observed in multiple central synapses is a pull–push type of control in which activation of receptors coupled to the G-protein Gs promote long-term potentiation (LTP) at the expense of long-term depression (LTD), whereas receptors coupled to Gq promote LTD at the expense of LTP. Notably, coactivation of both Gs- and Gq-coupled receptors enhances the gain of both LTP and LTD. To account for these observations, we propose a simple kinetic model in which AMPA receptors (AMPARs) are trafficked between multiple subcompartments in and around the postsynaptic spine. In the model AMPARs in the postsynaptic density compartment (PSD) are the primary contributors to synaptic conductance. During LTP induction, AMPARs are trafficked to the PSD primarily from a relatively small perisynaptic (peri-PSD) compartment. Gs-coupled receptors promote LTP by replenishing peri-PSD through increased AMPAR exocytosis from a pool of endocytic AMPAR. During LTD induction AMPARs are trafficked in the reverse direction, from the PSD to the peri-PSD compartment, and Gq-coupled receptors promote LTD by clearing the peri-PSD compartment through increased AMPAR endocytosis. We claim that the model not only captures essential features of the pull–push neuromodulation of synaptic plasticity, but it is also consistent with other actions of neuromodulators observed in slice experiments and is compatible with the current understanding of AMPAR trafficking.

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